This multimodality functional neuroimaging (PET and fMRI) study investigates the neurobiological basis of acupuncture analgesia. It is submitted in response to the National Center for Complementary and Alternative Medicine's call for R21 applications to investigate areas of specific interest to this institute. The goal of this application is to use a double-blind, sham-controlled experimental paradigm in a single cohort to determine both fMRI signal change during acupuncture administration and during acute noxious stimulation before and after acupuncture treatment and to perform quantitative characterization of endogenous opioid peptide release during acupuncture treatment. To accomplish this goal we will harness the power of high field, rapid acquisition fMRI to yield the high spatial and temporal resolution maps necessary for in-depth characterization of neuronal responses. We will use our novel magnet-compatible, mechanical and thermal stimulators to deliver noxious stimuli with precise timing and on-line psychophysical assessments to investigate the mechanism of pain intensity encoding and how this encoding is affected by acupuncture treatment. We will utilize PET and [11C]diprenorphine at baseline and during acupuncture to quantitate opioid receptor binding and thus indirectly measure endogenous opioid peptide release. We will determine in which brain regions opioid binding changes correlate with analgesia. Finally we will determine the relation between acupuncture-associated changes in endogenous opioid peptide release and the pattern of neuronal activity changes as evidenced in fMRI signal changes in specific brain regions. We have built into our study design the collection of physiological data in order to help bridge the findings from these experiments to both clinical practice and other, non-neuroimaging research studies. This application also responds to a recent Program Announcement, PA-99-021 that calls for efforts to "investigate both pharmacological and behavioral interventions to prevent pain". This application specifically directs efforts to address the needs outlined in that PA by refining neuroimaging paradigms for the study of functional correlates of pain perception. The proposed experiments will explore basic mechanisms of the conscious perception of pain and the affective responses to pain and attempt to elucidate the central nervous system mechanisms of acupuncture analgesia. This application in addition addresses another recent Program Announcement, PA-98-102 that calls for expansion of research on neuroimaging of pain, including analytical techniques for the study of structural and functional correlates of pain perception, particularly for diagnostic purposes.